环状 RNA 基因 RNF220 而非其线性同源基因 RNF220 调控细胞生长，并与儿童急性髓系白血病的复发相关。
CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid leukemia.
机构信息
Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Zhujiang Newtown, Tianhe District, Guangzhou, 510623, Guangdong, China.
出版信息
Mol Cancer. 2021 Oct 26;20(1):139. doi: 10.1186/s12943-021-01395-7.
BACKGROUND
Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML).
METHODS
Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a.
RESULTS
We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse.
CONCLUSIONS
Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction.
背景
环状 RNA（circRNAs）构成了具有独特结构的转录本家族，已被证实在肿瘤发生中具有重要作用，并且是潜在的生物标志物或治疗靶点。然而，在小儿急性髓系白血病（AML）中，只有少数 circRNAs 的功能得到了表征。
方法
在这里，我们使用 circRNA 微阵列研究了小儿 AML 中 circRNAs 的表达模式。评估了 circRNF220 的特征、潜在的诊断价值和预后意义。进行了一系列功能实验，以研究 circRNF220 在原代小儿 AML 细胞中的作用。然后，我们通过 RNA-seq 研究了 circRNF220 在原代 AML 细胞中调节的异常转录网络。此外，实施了生物素 RNA 下拉测定来验证 circRNF220 和 miR-30a 之间的关系。
结果
我们鉴定了一种特异性在小儿 AML 患者的外周血和骨髓中丰富并积累的环状 RNA，circRNF220。它可以高灵敏度和特异性地区分 AML 与 ALL 和其他血液恶性肿瘤。重要的是，circRNF220 的表达独立地预测预后，而 circRNF220 的高表达是复发的不利预后标志物。此外，我们表征了 circRNF220 的功能，发现 circRNF220 敲低特异性地抑制了 AML 细胞系和原代细胞的增殖并促进了凋亡。机制上，circRNF220 可能作为 miR-30a 的内源性海绵，通过与 miR-30a 结合并抑制其活性来发挥作用，从而增加其靶标 MYSM1 和 IER2 的表达，并与 AML 复发有关。
结论
总的来说，这些发现表明 circRNF220 可以高效且特异性地用于小儿 AML 的准确诊断，对预测复发具有意义。
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